Direct healthcare costs and their relationships with age at start of drug use and current pattern of use: a cross-sectional study

ABSTRACT BACKGROUND: It is well known that early start of drug use can lead users to psychosocial problems in adulthood, but its relationship with users’ direct healthcare costs has not been well established OBJECTIVES: To estimate the direct healthcare costs of drug dependency treated at a community mental health service, and to ascertain whether early start of drug use and current drug use pattern may exert influences on these costs. DESIGN AND SETTING: Retrospective cross-sectional study conducted at a community mental health service in a municipality in the state of São Paulo, Brazil. METHODS: The relationships between direct healthcare costs from the perspective of the public healthcare system, age at start of drug use and drug use pattern were investigated in a sample of 105 individuals. A gamma-distribution generalized linear model was used to identify the cost drivers of direct costs. RESULTS: The mean monthly direct healthcare costs per capita for early-start drug users in 2020 were 1,181.31 Brazilian reais (BRL) (274.72 United State dollars (USD) according to purchasing power parity (PPP)) and 1,355.78 BRL (315.29 USD PPP) for late-start users. Early start of drug use predicted greater severity of cannabis use and use of multiple drugs. The highest direct costs were due to drug dependence combined with alcohol abuse, and due to late start of drug use. CONCLUSIONS: Preventive measures should be prioritized in public policies, in terms of strengthening protective factors before an early start of drug use.


INTRODUCTION
The prevalence and incidence of drug use in Brazil have increased over recent years, and the age at the start of use has become much lower than in the past. 1,2 The Second Brazilian National Survey on Alcohol and Drugs (Levantamento Nacional de Álcool e Drogas, LENAD) showed that among adolescents aged 14 to 17 years, 4.3% were frequent users of cannabis in the past year, 2.3% were frequent users of cocaine, 0.8% frequently used crack and 60% had used alcohol before their 15 th birthday. 2 Additionally, Brazil is ranked as the second largest cocaine market in the world, and national consumption accounts for 20% of the world's cocaine market. 3,4 Early drug use during adolescence is deleterious for the brain maturation process 5,6 and has both short and long-term health consequences, [5][6][7][8][9] including cognitive impairment, 10 substance use disorder, 9 reduced educational and occupational attainment 7,8 and engagement in illicit activities. 11,12 In this regard, preventive programs have been widely implemented for reducing drug use among adolescents and, consequently, for avoiding economic and social costs. [13][14][15] The great economic impact of substance-related disorders on individuals and society was demonstrated through a study on the burden of diseases in Brazil. 16 This showed that, among the diseases that contributed most to disability-adjusted life years (DALYs) in this country, disorders relating to use of alcohol and other drugs jumped from third place in 1990 to first in 2016 among men, and from tenth to seventh among women, over the same period. Furthermore, substance-related disorders have been indicated to be one of the costliest health conditions for a healthcare system, [17][18][19] especially regarding hospitalization. 20 In Brazil, there is a lack of data on the costs according to different drug users' profiles, especially considering their relationship to age at the start of use. The long-term economic impact of early drug use on the healthcare system needs to be examined.
Through this, public healthcare managers can be supported in their decision-making process with regard to allocating the available public healthcare resources more effectively, for prevention and treatment strategies. In this study, we hypothesize that an early start to drug use might be a predictor of higher direct costs for the public healthcare system.

OBJECTIVES
The aims of this study were to estimate the direct costs due to treatments for individuals dependent on alcohol and other drugs, at a public community mental health service; and to ascertain the potential influences of age at the start of drug use and current drug use pattern on direct healthcare costs. In addition, the potential economic consequences for the public healthcare system were discussed.

Study design
This was a retrospective cross-sectional study on the relationships between direct healthcare costs and age at the start of drug use and drug use pattern, among individuals undergoing treatment for substance-related disorders at a community mental healthcare service. The cost analysis was conducted from the public healthcare perspective. This study was approved by

Setting and participants
The study sample consisted of 105 subjects with a pattern of moderate-to-severe alcohol/drug use who were undergoing treatment at a public community mental health service, the Psychosocial Care Center for Users of Alcohol and Other Drugs (Centro de Atenção Psicossocial para usuários de álcool e outras drogas -CAPS-ad) in the city of Rio Claro, state of São Paulo, Brazil.
CAPS-ad is a community-based mental health service that promotes public comprehensive care for people aged 18 years or over with substance-related disorders. It is the reference for substance-related treatment within the public healthcare network in Brazil. This CAPS-ad serves the population of the city of Rio Claro and another four small neighboring municipalities, covering a demographic area with 216,000 inhabitants. The service has a multiprofessional healthcare staff of two psychiatrists, one general practitioner, one nurse, two nursing technicians, two psychologists, two occupational therapists and one social worker. 21 The inclusion criteria were that the subjects need to be aged 18 years or older, be undergoing treatment at CAPS-ad, be able to understand the interviewer's questions and meet the criteria for a pattern of moderate or severe drug use with regard to at least one drug, i.e. 11 points or more for alcohol use and 4 points or more for cannabis, alcohol and cocaine/crack use, in accordance with the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST).

Early and late-onset drug use
Subjects who began using alcohol, cannabis, cocaine or crack at age 15 years or younger were classified into the "early onset" drug use group. Subjects who started using these drugs at age 16 years or later were classified into the "late onset" drug use group.
There is no cutoff age that defines early and late onset of drug use in the literature. It was suggested in some previous studies that this cutoff point could be defined according to the epidemiological data on drug use of the region studied. 9,22 In some developed countries, "early onset" drug use has been considered to be use that occurs up to the age of 17 years and "late onset" as use that occurs at the age of 18 years or later. 9 However, a Brazilian national survey from 2012 showed that the onset of drug use occurred at a much earlier age in this country. 1,2

Data collection
Data on direct health costs were collected using a "bottom-up" approach based on patient-level microdata, through application of the Brazilian version of the Client Socio-Demographic and Service Receipt Inventory (CSSRI), 23,24,25

Direct healthcare costs
Data on direct costs were collected for the 30 days preceding participation in this study, in relation to the following components: • CAPS-ad healthcare staff care comprised home visits; visits to psychiatrists and general practitioners; and individual and group sessions with occupational therapists, psychologists, social workers and nurses and nurse assistants.
• Medications included psychotropic and non-psychotropic medicines.
• Hospital care incorporated care received in psychiatric and general hospitals.
• Outpatient care included CAPS-III, which has the same CAPS-ad service structure but an around-the-clock service, 24 hours a day and 7 days a week, with crisis support beds for all cases of mental disorders in its coverage area. This also included non-psychiatric medical specialty outpatient services and dental assistance outpatient service.
• Primary care included primary care provided by nurses and doctors.
• Transport included bus tickets to CAPS-ad, emergency mobile  28 Costs in Brazilian reais (BRL) were also converted to United States dollars (USD) using purchasing power parity (PPP) exchange rates. 29 The unit cost values were calculated by means of a top-down approach, in accordance with municipal accounting data provided by the local public healthcare manager. 30 For situations in which these data were not available, the current scientific literature was consulted. 31,32 Unit costs for medications were estimated from information provided by the municipal government regarding the prices paid for these medicines in the year 2015. For some medicines used by the subjects, the purchase prices were not available from the municipal government. In such situations, the medication prices database, 33 a Brazilian database on prices paid by the public healthcare sector for purchases of medicines, was consulted.

Data analysis
Initially, descriptive analysis was conducted. This was followed by an analysis on associations between variables and early and late onset of drug use. Associations between nominal variables were verified using the chi-square test or, in cases of small samples, Fisher's exact test. Student's t test was used to compare mean costs and the nonparametric Mann-Whitney test was used to compare numerical variables of non-normal distribution.
Inferential analysis was then conducted, in which "direct cost" was defined as the dependent variable in a gamma-distribution generalized linear model (GD-GLM) with a log binding function and marginal gamma distribution. 34 This model was chosen because of the nature of the dependent variable which was numerical, with non-negative values and asymmetry. The reasonableness of choosing this distribution was verified using Anscombe residuals. 34 The GD-GLM had two sequential stages of analysis: univariate and multivariate. For the univariate analysis, variables that demonstrated significant associations (a significance level of 5% or P ≤ 0.05) with the age of onset of drug use and those that we intended to investigate as possible direct cost predictors were selected. Predictive variables that showed associations with the dependent variable at a significance level of 20% in the univariate analysis, except for the current age and time of treatment (control variables), were selected for the multivariate models. For the predictive variables present in numerical and categorical forms that were both significant in the univariate model, the form in which the association with the dependent variable was more significant was selected. Subsequently, the variables that did not present significance at the 5% level were excluded one by one, in order of significance, using the backward method. The analyses were performed using the STATA 12 (StataCorp, Texas, 2011) 35 statistical package.

RESULTS
Totals of 59 early-onset substance users (56.2%) and 46 lateonset substance users (43.8%) composed the study sample (n = 105). The mean ages at onset of alcohol, cannabis, cocaine and crack use were, respectively, 15.2 years (standard deviation, SD = 5.7), 15.6 years (SD = 5.6), 20.2 years (SD = 8.6) and 23.9 years (SD = 12). Table 1 shows the sociodemographic profile of the sample according to early or late onset of drug use. The mean age of the entire sample was 42.7 years (SD = 11.0), and there was a significant difference (P = 0.01) between the ages of the early-onset group (40.5 years; SD = 11.0) and the late-onset group (45.6 years; SD = 9.4). On average, early-exposed users were five years younger than the late-exposed users. The mean length of time spent undergoing the current treatment at CAPS-ad was 46.4 days overall (SD = 87.8). For the early-onset group, this number was 42.2 days (SD = 83.7) and for the late-onset group it was 51.7 days (SD = 93.6) (P = 0.58). Table 2 presents data on past and current drug use patterns, as measured through ASSIST, according to early or late onset of sessions with psychologist (P = 0.01), nurse routine individual care sessions (P = 0.00) and bus ticket to CAPS-ad (P = 0.04), in comparison with the early-onset group.  This latter group had a higher number of subjects who met the criteria for abuse and possible dependence on cannabis, compared with the group of late-onset users (P = 0.04).       first drug experimentation occurred there was a 1.1% increase in total direct cost.
In addition, treatment for drug dependents who were also alcohol abusers was 4.4 times more expensive than for dependents who did not use alcohol, and treatment for alcohol-dependent users was twice as expensive as for those who did not use alcohol. Drug dependents who were also alcohol abusers had a higher monthly average direct cost (BRL 2,247.53, i.e. USD 522.68 PPP, per capita in 2020) than that of drug dependents who only made occasional use of alcohol (BRL 471.06, i.e. USD 109.54 PPP, per capita in 2020) (P = 0.002), as can be seen in Table 7.

DISCUSSION
The direct costs were higher for the subjects who met the criteria for both drug-related dependence and alcohol abuse, and were also higher among those in the late-onset group. One potential   these data indicate that, as is also occurring in other countries like Spain, 40 the age at which cannabis experimentation starts is becoming similar to the ages at which alcohol and tobacco use start. This same study also showed that cannabis use acted as a predictor of alcohol use and had significant relationships with subsequent use of cocaine, prescription opioids and tranquillizers.
Therefore, these data can inform policymakers and society about the risks of early-onset cannabis use, considering the important role that early-onset use of this drug could be playing in predicting subsequent abuse of and dependence upon multiple drugs.
These data also reinforce the notion that preventive measures should be prioritized in substance-related national policies in terms of strengthening protective factors before early-onset drug use might occur, and in the interests of preventing further severe and multiple drug use.
In 2013, three public preventive programs targeting drug use were implemented in Brazil. 41 However, no official data exist in relation to the implementation costs of these programs; moreover, the effectiveness of only one of these programs, the #TamoJunto program, has been evaluated. Sanchez et al. 42  The current drug use situation in Brazil has alerted healthcare workers and government officials to the need to estimate its economic impact on the Brazilian public healthcare system in order to develop specific public policies, especially focused on prevention, targeting the highest risk groups. Public policies oriented toward preventing early-onset drug use among adolescents may reduce the economic impact that substance-related disorders have on the public healthcare system. These may also help adolescents avoid both developing dependence upon multiple drugs and having their consequences in adulthood.
There are several limitations to this study. Two related limitations comprised the small sample size and low representativeness of all the alcohol and drug users' profiles. This indicates that caution is needed in making generalizations. Another limitation was the retrospective study design, which did not permit analysis of possible cost variations according to each user's profile from his or her age at the onset of drug use to the age at the time of participation in this study. Lastly, there was some uncertainty regarding inaccuracies of cost estimations, given the large territorial extent of Brazil and regional differences in values aggregated to the components of the costs considered.

CONCLUSIONS
Our results are useful for alerting policymakers towards addressing national preventive policies against drug use, for the young population. Preventive measures should be prioritized within national alcohol and drug policies, in order to strengthen protective factors before early onset of drug use, especially regarding alcohol and cannabis, and to avert further severe and multiple drug use. Therefore, our findings suggest that there is a need to conduct further prospective studies on adolescents' drug use, their pathways through the healthcare system, the costs of their drug use and the social outcomes among these individuals.